An accurate assessment of the efficiency of blood coagulation (thromboelastography) is very important for treating hemorrhage, trauma, as well as for various anesthetic and surgical procedures.
Coagulation is the process whereby blood forms clots. Blood coagulation, i.e., thrombogenesis, is a result of a series of biochemical reactions through primary hemostasis and secondary hemostasis. Briefly, primary hemostasis involves platelets adhesion and aggregation; secondary hemostasis involves plasma factors reacting with each other and fibrinogen being converted into cross-linked polymeric fibrin through several enzymatic reactions. Blood coagulation is the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin the repair of damaged vessel. Disorders of this coagulation can lead to an increased risk of bleeding (hemorrhage) or obstructive clotting (thrombosis).
The coagulation usually begins almost instantly after an injury to the blood vessel has damaged the endothelium lining the vessel. Exposure of the damaged vessel wall to the bare tissue in the wound led to initiation of coagulation by tissue factor expressed as an integral membrane protein. Tissue factor binds to plasma factor VIIa initiates enzymatic reactions of procoagulant plasma proteins that lead to the formation of thrombin resulting in platelet activation and subsequent assembly of procoagulant complexes on the platelet surface leading to the conversion of fibrinogen to cross-linked fibrin clots which strengthen the platelet plug. This coagulation cascade is regulated tightly by various endogenous anticoagulants that act at different steps in the pathway to maintain the balance between clotting and bleeding.
Conventional coagulation assays have poor predictive accuracy for surgical bleeding and coagulopathy caused by traumatic injury and hemorrhage. These assays are generally performed in vitro without platelets and other blood cells; and also not able to test hemostasis function for hypothermic patients. With these conventional approaches, the pathophysiology of bleeding associated with trauma coagulopathy and of massive intraoperative blood loss cannot be clearly differentiated, thus making substitution of blood products difficult. Trauma is one of the leading causes of death worldwide. Hemorrhage is responsible for 40% of trauma caused deaths. Coagulopathy associated with severe injury complicates the control of bleeding and is linked to the increased morbidity and mortality in trauma patients. Rapid diagnosis and directed interventions may reduce preventable deaths after severe injury. The causes of coagulopathy in patients with severe trauma are multifactorial, including consumption and dilution of platelets and coagulation factors, as well as dysfunctions of platelets and the coagulation system. Hypothermia, acidosis, and dilution from standard resuscitation can worsen the presenting coagulopathy and perpetuate bleeding. Strategies to prevent significant coagulopathy and to effectively control critical bleeding in the presence of coagulopathy may reduce the requirement for blood transfusion, thereby improving clinical outcome of patients with major trauma.
In addition, the hemorrhage in traumatized casualties remains the major cause of death in combats. A rugged device to assess overall hemostasis function in forward combat areas is thus strongly desired. Also, perioperative diagnosis and monitoring of blood coagulation is critical to better understand the causes of hemorrhage, to guide hemostatic therapies, and to predict the risk of bleeding during the consecutive anesthetic or surgical procedures. For patients undergoing major surgery, or under urgent situations such as trauma, hemorrhage, stoke or sepsis, a timely informed blood coagulation assessment is critically needed in determining patient susceptibility to postoperative thrombotic complications or as indicator of early sepsis, particularly regarding the use of blood products and guiding treatment with haemostatic components.
Concerning the test of thromboelastography, usually a small sample of blood (typically 0.36 ml) is placed into a cuvette that is rotated gently through 4° 45′ (cycle time 6 min) to imitate sluggish venous flow and activate coagulation. When a sensor is inserted into the sample, a clot will form between the cuvette and the sensor. The speed and strength of the clot formation can be measured in various ways; and are dependent on the activity of the plasmatic coagulation system, platelet function, fibrinolysis and other factors which may be affected by illness, environment and medications. If there is suspicion that the blood has difficulty to clot due to either medication or disease, the blood sample would be exposed to a clot-inducing agent (such as kaolin) immediately prior to the test.
The first thromboelastography method was introduced by Hartert in 1948 and certain modifications have been made over the years to improve the technique. Hartert introduced a cylindrical member rigidly mounted in the solid frame and a beaker mounted on the upper end of a rod-like support that is mounted onto the solid frame by means of a circular resilient diaphragm. A coil arrangement at the lower end of the rod produces a rotating electro-magnet field and imparts to the rod an orbital movement. A further core above the diaphragm is used as the pick-up device to record trace of the change in amplitude of the elastic support upon clot formation. This allows more detailed and accurate recording of the clot formation process. Haemoscope Corporation further improves the technique and includes a torque sensing column and a drive ring disposed around a body of the column. The apparatus further includes a first guide shaft rigidly secured to the drive ring and a cup holder. This invention led to the current Haemoscope TEG device.
Advances in technology have led to certain developments of thromboelastography techniques. The TEG® device (Haemoscope Corporation, IL, USA) and ROTEM® device (Pentapharm Gmbh, Germany) both measure clot viscoelasticity and provide the rate, strength and stability of clot formation, as well as fibrinolysis process in patients at perioperative clinical settings to guide resuscitation particularly regarding to the use of blood products. However, current TEG® and ROTEM® technologies both use fragile moving parts (either a rotating pin or a rotating cup) and sophisticated mechanical assemblies which made the devices difficult to use at a point-of-care setting or in combat areas under war conditions. The detection signals used in the current TEG® and ROTEM® technology are obtained either by torsion wire or by light change reflected on a moving mirror. Disadvantages of the current TEG® or ROTEM® technology also include low precision, low sensitivity (signal-to-noise ratio), and interference from vibration, limited transportability and difficulty of handling whole blood samples.
Other techniques have also been developed to detect blood elasticity changes upon clot formation. Among them, the Sonoclot Analyzer (Sienco Inc., Arvada, Colo.) uses a hollow, open-ended disposable plastic probe mounted on a transducer head where the probe oscillates vertically during testing. The changes in impedance to movement imposed by the developing clot are recorded. However the Sonoclot test trace has been considered as rather qualitative in its clinical applications.
Moreover, the maximal clot firmness of these techniques is about 50 to 70 mm. Considering that a general sensitivity level is about 2 mm, higher test-to-test variations are almost unavoidable. This is a serious problem, especially in the case of measuring samples in thrombocyte inhibited tests for fibrinogen abnormality.
So far there is not a simple, reliable and rapid diagnostic test that allows clinicians to manage massively transfused blood accurately at the bedside, and to timely monitor hemostasis status, to effectively manage the associated bleeding and make correct diagnosis and optimal use of blood products.
It is therefore an objective of the present invention to provide a quick and easy device and method for performing blood thromboelastographic assay, particularly measuring blood clot formation, rate of clot formation, clot strength and degree of blood fibrinolysis.